The
body's inability to grow new tissue as it ages might be overcome by
increasing the activity of a gene known as FoxM1B, according to a study
published in the Sept. 25 issue of the Proceedings of the National Academy
of Science.

By
increasing the activity, or expression, of this gene in aged experimental
mice, Robert Costa, professor of molecular genetics at the University
of Illinois at Chicago College of Medicine, and his colleagues were
able to restore the regeneration of liver cells to rates of growth typical
of young mice.

Because
in humans the FoxM1B gene exists not only in the liver but also throughout
the body, the researchers believe their discovery might one day be used
in gene therapy in the elderly to restore their ability to replace old
cells with new ones and rejuvenate worn-out organs. Cells divide normally
when stimulated by FoxM1B, making it an ideal candidate for use in therapeutic
intervention, according to Costa.

"Ponce
de Leon was looking in the wrong place for the fountain of youth," said
Costa. "He should have been looking for the FoxM1B gene."

According
to Costa, earlier studies had shown that age-related defects in the
proliferation of cells found in connective tissue throughout the body
are associated with diminished expression of FoxM1B. Defects in cell
proliferation lead to chromosomal abnormalities and mutations, which
in turn lead to a variety of health problems found in older people,
including infections, organ failure, Alzheimer's disease, dementia and
an increased incidence of cancer.

In
the elderly, cells grow slowly in response to injury and do not proliferate
adequately to replenish damaged cells in the skin, hair, muscle and
other tissues. As a consequence, injuries take longer to heal, and certain
physical changes occur-for example, the skin wrinkles and muscles atrophy.

In
the present study, aged mice were fitted with a "promoter" to increase
expression of the FoxM1B gene. After undergoing a partial hepatectomy,
in which a portion of the liver was removed, the mice rapidly regenerated
new tissue, unlike typical aged mice.

The
DNA in the regenerating liver cells replicated normally, and cells divided
just as they do in the livers of young mice that have been injured.
Furthermore, laboratory studies showed that increasing expression of
the FoxM1B gene in aged mice restored as well the activity of numerous
other genes involved in cell division.

"FoxM1B
clearly regulates the expression of a whole network of genes that are
required for cells to multiply," said Costa.

Importantly,
Costa added, the study indicated that the FoxM1B gene also controls
exit from mitosis, that is, the completion of cell division. Without
that, cells would be abnormal, failing to divide and retaining too many
copies of DNA - defects commonly seen in cancers.

Other
scientists involved in the study were Xinhe Wang, from UIC, Elizabeth
Quail, a visiting scientist from the University of Western Australia,
Nai-Jung Hung, from UIC, Yongjun Tan, from UIC, and Honggang Ye, formerly
from UIC and now at the University of Chicago.